tbuckley/cabot-search huggingface dataset:
Cancer-related fatigue and functional impairment: Retrospective study in patients with newly diagnosed solid-tumor cancer.
Authors: Dori Michelle Beeler, Danielle Boselli, Patrick L. Meadors, Declan Walsh
Journal: Journal of Clinical Oncology (2023)

e24143 Background: Functional impairment (FI) and debilitating cancer-related fatigue (CRF) occur across all cancers with negative impact on quality of life (QoL). The nature of the association between CRF and FIs is unknown. We conducted a retrospective, single institutional study to investigate the association between CRF and FIs prior to treatment in newly diagnosed solid tumors within Levine Cancer Institute (LCI), a regional, multi-site cancer system. Methods: Electronic Distress Screening (EDS) and Cancer Registry databases from Jan 2017 to Jan 2022 were sourced. CRF was defined as fatigue (0-10 scale) ≥4. FIs were assessed using three EDS questions with a two-week recall: (1) how well have you been able to manage your day-to-day life? (PM); (2) has your physical health kept you from doing things like household chores or climbing stairs? (PHL); and (3) do you have limited movement (LM) in any of the following [body parts]? These are proxies for activities of daily living and instrumental activities of daily living. LCI patients aged ≥18 years with one cancer diagnosis within 10 years, completed EDS ±2 weeks of diagnosis, and before treatment were included. Proportions were compared using Fisher’s Exact test; multivariable logistic regression models evaluated the prognostic value of FIs on CRF. Results: 3439 unique patients were identified with strong associations between CRF and FIs. Median age was 62 years (18 to 97); 68% female and 78% White. The largest diagnostic groups were breast (30%), upper GI (17%), and gynecologic (16%); and 21% had stage IV disease. High CRF was reported by 57% (N = 1946) patients. FIs included: poor PM of day-to-day life, PHL, and ≥1 one body area of LM which were reported by 18% (N = 613), 19% (N = 648), and 29% (N = 982) respectively. More patients with FIs indicated CRF: PM 92% v. no PM 49% (P &lt; .01), PHL 92% v. no PHL 48% (P &lt; .01), and LM 75% v. no LM 49% (P &lt; .01). In multivariable modeling, all FIs were significantly associated with CRF. The Table outlines that all lower bounds of estimated 95% confidence intervals ratios associated with odds ratios were greater than 1.66 when adjusted for age at diagnosis, sex, race, diagnostic group, and advanced disease, highlighting that all are independently associated with CRF. Conclusions: FIs are highly associated with CRF prior to treatment for solid tumors in a large cohort of patients. Pre-diagnosis FI screening identifies patients at risk for significant CRF. Early CRF management is essential to reduce negative QoL impacts.[Table: see text]
Characteristics of SARSCOV2 infection in vaccinated patients with cancer in one Latin American country: Real world evidence from ACHOCC19-VAC study.
Authors: Aylen Vanessa Ospina Serrano, Ricardo Elias Bruges Maya, Isabel Munevar, Paola Jimenez, William Armando Mantilla, Pedro Ramos, Giovanna Patricia Rivas Tafurt, Mirian Caicedo, Sandra Aruachan, Ana Cristina Avendaño, Ray Manneh Kopp, Ivan Triana, Angela Barrero
Journal: Journal of Clinical Oncology (2023)

e18806 Background: According to results of previous ACHOC-C19 study, mortality in patients with cancer and COVID 19 infection in Colombia is 26%. The impact of vaccination was not evaluated prior to the implementation of this strategy worldwide in patients with cancer. We aimed to characterize SARSCOV 2 infection in a local cohort of vaccinated oncologic patients. Methods: The ACHOCC-19 VAC registry is a national multi-center observational cohort study. Data were collected between April 2021 and March 2022. Inclusion criteria were: age more than 18 years, confirmed diagnosis of cancer (solid tumors), be receiving treatment or being followed-up and have received at least one dose of COVID-19 vaccine. 11 oncologists from 10 health institutions participated. The primary outcome was 30 days mortality due to COVID 19 infection. Secondary outcome was to describe adverse effects related to vaccination. A descriptive univariate and inferential analysis were performed. Results: 720 patients were included, average age was 60 years, 91% lived in urban areas, 12% had low income. 73% (525) were women. The most frequent diagnosis were: breast cancer 47% (338), prostate cancer 7% (50) and lung cancer 4.6% (36). ECOG 0-1 and 2 in 91.7% and 6.1% of population respectively. 41.40% had no comorbidities and 59.4% had 1 or more comorbidity. 29.1% presented metastatic cancer, 59.3% were receiving oncological treatment of which, 32.7% were neoadjuvant or adjuvant and 28.6% palliative. 31.66% were being followed up without treatment. 32.6% had stable disease and 5.9% had cancer in progression. Administered vaccines were CoronaVac (40%), BNT162b2 (35%) others 25%, in accordance with initial availability of vaccines for oncologic population in Colombia. 93.9% of population received 2 doses. COVID19 infection was acquired by 35.9% of the population, 30 days mortality due to infection was 3%. Table 1. Frequency of adverse effects with first and second dose were 14.8% and 12.2%, mild intensity in 93% and 100% respectively, being myalgias (5%), arthralgias (2-3%) and fever (3.5%) the most frequent. Conclusions: In our population, the efficacy of the vaccine against COVID 19 is consistent with available reports in the scientific literature. The incidence of 30 days mortality due to SARCOV 2 infection is very low. Vaccine-related adverse effects had frequency of less than 15% and mild intensity. These findings reinforce the need to promote and intensify vaccination in the oncologic patients. [Table: see text] [Table: see text]
Real-world experience of checkpoint inhibitors across India: CRSF 2020-01.
Authors: Gautam Goyal, Arun Chandrasekharan, Manuprasad Avaronnan, Vikas Talreja, Bharatsinha Baburao Bhosale, Rushabh Kothari, Tanmoy Mondal, Nikhil Pande, Avinash Talele, Bhavesh Pradip Poladia, Vivek Agarwala, Ashay Karpe
Journal: Journal of Clinical Oncology (2023)

e18862 Background: There are limited data available from India on the real-world use of checkpoint inhibitors. Hence we did this analysis across India to study the pattern of use and outcomes with checkpoint inhibitors. Methods: This was a retrospective multicentric protocol. Patients who received immunotherapy from January 2016 to October 2021 were included. The baseline demographic, previous treatment, response, date of progression, date of death and status were noted. SPSS version 20 was used for analysis. Descriptive statistics were performed. Kaplan Meier method was used for estimation of progression-free survival (PFS) and overall survival (OS). COX regression model was used to identify factors impacting OS. Results: We identified 308 patients in the study. The median age was 58.5 years (Interquartile range 51-66 years) and there was a male preponderance (249, 80.8%). The 3 commonest sites of use were head and neck cancer in 144 patients (46.8%), lung cancer in 81 (26.3%) and renal cell carcinoma in 31(10.1) patients. The ECOG PS was 0-1 in 215 (70%), 2 in 71 (23.1), 3-4 in 21(6.8%) and not documented in 1(0.3%) patient. The two most common checkpoint inhibitors used were nivolumab and pembrolizumab 255 (82.8%) and 37(12%) patients respectively. These were used in curative setting in 6 patients (1.9%) and palliative in rest all. 43(14%) patients received them as first-line in, 129 (41.9) as second-line and beyond the second line in 130 (42.2%) patients. The response rate was 24% (n = 74). The median PFS was 4.067 (95%CI 3.45-4.67) and the median OS was 10.0 months (95%CI 6.2-13.8). Among the factors tested for impact on OS the ECOG PS 0-1 ( HR-0.493 95%CI 0.324-0.749; P = 0.001), non head and neck site of the disease (HR-2.134 95%CI 1.164-3.911) and reception of immunotherapy in first line setting (HR -0.533 95%CI 0.295-0.963: P = 0.037) had an favorable impact on OS. Conclusions: Checkpoint inhibitors provide similar efficacy as those seen in pivotal studies in real-world settings.
Characterizing of adverse events across 30,000 peer reviewed case report publications.
Authors: Suad Khabbaha, Sarah Carder Dempsey, Aranka Anema, Sonal Singh, Kristian Thorlund
Journal: Journal of Clinical Oncology (2023)

e18858 Background: Pharmacovigilance suffers from considerable underreporting. This is particularly the case for novel oncology therapeutics where regulatory approval is supported by clinical trials with small sample sizes and limited follow-up to observe later treatment-related adverse events. More recently approval of oncologic therapies based on Real World Evidence, using study designs such as historical controls further complicates the task of assessing the clinical significance of AE. Furthermore, causation is rarely confirmed outside controlled settings such as clinical trials, and particularly absent in conventional RWE sources. Methods: We evaluated the ability of published case reports to serve as a source of pharmacovigilance for novel oncology therapeutics as well as the prevalence of reporting of clinician confirmed causality. We assessed structured patient journey data extracted from approximately 30,000 peer reviewed oncology case reports published since 2015 and available from the OpenCaseTM database. The reviewed cases covered hematological cancers (myelomas, leukemias, and lymphomas) and solid cancers (lung, breast, colorectal, and bladder) and represented case reports from over 125 nations. Adverse events and key patient journey data were extracted using state-of-the-art natural language processing (NLP) models with validated accuracy of over 92%. Results: A total of 58.5% reported at least one adverse event after or during a treatment period. Of these, the median number of reported adverse events were 4 (IQR: 2 - 8). There were 12,551 unique AEs after normalizing with the MedDRA database using a state-of-the-art AI model. The ten most frequently reported AEs were pain, fever, weight loss, fatigue, post-op complications, fatigue, anemia, infection, bleeding, and dyspnea, ranging from 897 to 2606 occurrences. Clinical confirmation of causation (i.e., treatment-related adverse event) was available for at least one adverse event in over half of the case reports. The majority of these were related to immune checkpoint inhibitors, but toxicity due to chemotherapies and complications due to surgery were also common. Conclusions: In conclusion, our study suggests that peer reviewed oncology case reports represent a rich source of reported adverse events, often with clinically confirmed causality, which could substantially augment adverse events reporting of oncology therapeutics.
Plasma cell-free RNA PD-L1 expression and survival with immune checkpoint inhibitor-based treatment in advanced non-small-cell lung cancer.
Authors: Paul R. Walker, Sriraksha Jayananda, Melisa Pasli, Mahvish Muzaffar
Journal: Journal of Clinical Oncology (2023)

e21090 Background: Tissue PD-L1 protein expression is predictive of immune checkpoint inhibitor (ICI)-based treatment outcomes in advanced non-small-cell lung cancer (aNSCLC). However, tissue PD-L1 can be fraught with tissue acquisition difficulties and tumor heterogeneity. Plasma cell-free RNA (cfRNA) PD-L1 expression assessed with a liquid biopsy potentially overcomes these tissue limitations and could identify additional patients likely to benefit from ICI therapy. Outcome studies validating this novel approach have not been previously reported. Methods: An observational cohort of patients with aNSCLC treated in an academic medical center with 1 st -line ICI-based therapies were retrospectively evaluated for a pre-planned endpoint of overall survival (OS) based upon plasma cfRNA PD-L1 expression by a proprietary exosome-free real-time qPCR assay and/or tissue PD-L1 protein expression (Dako 22C3) performed in commercial CLIA/CAP accredited laboratories. Results: Of 75 consecutive aNSCLC patients, 16 (21.3%) were plasma cfRNA PD-L1 positive expression with 6 of these 16 (37%) tissue PD-L1 negative or quantity not sufficient. 35 patients were both tissue and plasma PD-L1 negative and 24 patients tissue PD-L1 positive but plasma PD-L1 negative. Median follow-up 34 months. The plasma PD-L1 or tissue PD-L1 positive patients demonstrated no difference in OS outcomes (median OS 16 months; 3-year landmark OS 30%; hazard ratio (HR) 0.97; 95% CI, 0.44-2.10). The plasma PD-L1 positive patients demonstrated superior OS outcomes compared to tissue and plasma PD-L1 negative patients (median OS 16 months versus 8 months; landmark 3-year OS 30% versus 20%; HR 0.59; 95% CI, 0.31-1.11). The plasma PD-L1 positive patients demonstrated no differing OS outcomes whether tissue PD-L1 positive or negative (median OS 13-16 months; 3-year landmark OS 30%; HR 1.15; 95% CI, 0.32-4.05). Conclusions: In this single-institution aNSCLC patients receiving 1 st -line ICI therapy OS outcomes were the same for plasma PD-L1 positive patients vs. tissue PD-L1 positive patients. OS outcomes were superior for patients with positive plasma PD-L1 expression vs. similarly treated patients negative for tissue PD-L1 or plasma PD-L1 expression. In patients with plasma cfRNA PD-L1 expression, there was no OS differences whether tissue PD-L1 protein was positive or negative, suggesting that liquid biopsy might identify additional patients who could benefit from ICI therapy.
Geriatric-assessment-guided interventions for older adults with multiple myeloma: A feasibility study.
Authors: Christopher Edward Jensen, Kirsten A. Nyrop, Maya Logan, Martha Dell Strayhorn, Allison Mary Deal, Jordan Miller, Hyman B. Muss, Eben I. Lichtman, Sam Rubinstein, Sascha Alexander Tuchman
Journal: Journal of Clinical Oncology (2023)

12065 Background: Multiple myeloma (MM) is disproportionately a disease of older adults, and aging-related impairments are common in this population. Geriatric assessment (GA) guided supportive care programs have been linked to improved treatment outcomes among older adults with solid-organ cancers. We sought to evaluate the feasibility of a GA-guided supportive care program among older adults treated for MM. Methods: We leveraged an existing registry of adults with plasma cell disorders at the University of North Carolina. Registry participants meeting inclusion criteria were offered referrals to supportive care resources by their MM provider during routine visits in 2021-2022. Inclusion criteria were diagnosis of MM, age ≥60, and presence of ≥1 selected problem areas (physical function, polypharmacy, mental health) on the GA. Function deficits were defined as self-report of requiring assistance with ≥1 instrumental activities of daily living or recent fall(s), polypharmacy as ≥10 daily medications, and anxiety/depression on the Mental Health Index 13. Individuals with physical function deficits were offered referral to physical therapy (PT). Those with polypharmacy were offered referral to an oncology Clinical Pharmacist Practitioner (CPP) for comprehensive medication reconciliation and evaluation for de-prescribing. Patients with mental health symptoms were offered referral to our center’s Comprehensive Cancer Support Program (CCSP). Results: 59 individuals were identified as having at least one deficit on the GA (Table). Of these, 14 were already utilizing all relevant resources, leaving 45 individuals eligible for a new resource. Among these, 16 accepted a referral to at least one resource. An additional 16 were approached and declined all offered referrals. For the remaining 13 screened individuals, providers were prompted regarding a referral recommendation prior to the patient’s visit, but a referral was not offered during the visit. Physical therapy was the most commonly identified relevant resource (n = 46), followed by CPP visits (n = 33). Referral acceptance rates were highest among those recommended for a pharmacy visit (55% of those approached) and lowest for CCSP (0%). Conclusions: Given the prevalence of polypharmacy or physical function deficits and acceptance rates for related interventions, future interventions focusing on collaboration with CPPs or physical therapists appear feasible in this setting. Methods to direct patients to supportive care resources that do not rely on provider recommendations during the limited window of clinic visits may also be beneficial. Clinical trial information: NCT04999085 . [Table: see text]
Cardiovascular comorbidities and cardiovascular events in patients with metastatic prostate cancer.
Authors: Mohammed Alaeddine Saidi, Ghomari Soumeyya, Sarra Sedjelmaci
Journal: Journal of Clinical Oncology (2023)

e18851 Background: Prostate cancer (PCa) is globally the second most frequently diagnosed cancer in men. Patients with metastatic disease require cancer treatment for several months or even years. These treatments can have different side effects including adverse cardiac effects because of decreased serum testosterone levels. Methods: We conducted an observational study of men who were diagnosed with metastatic PCa from January 1, 2013, through December 31, 2018, with follow-up through December 31, 2022. We documented comorbid conditions, medications, tumor characteristics, type and duration of systemic treatment received. We also documented fasting glucose, total cholesterol, HDL, LDL and triglyceride levels at diagnosis. A cardiovascular event was defined as the first occurrence of hypertension, myocardial infraction, atrial fibrillation, heart failure, sudden cardiac death, acute thrombo-embolism and stroke. Cox proportional hazards models were used to assess association between cancer treatment and incident cardiovascular disease (CVD). Results: The cohort included One hundred and twenty one men who were diagnosed with metastatic prostate adenocarcinoma with a mean age at diagnosis of 68.9 years. 84.2% had bone-only metastasis. 69.4% had at least one CVD-Risk Factor. 53.4% Hypertension, 28.2% Dyslipidemia, 12.3% Diabetes. 15 men (12.3%) had pre-existing CVD. 3.3% stroke, 4.1% myocardial infraction, 2.4% heart failure, 2.4% atrial fibrillaton. 24.2% were under statin therapy and 22.0% under aspirin. Androgen deprivation therapy (ADT) was used for all patients, including 9.9% goserelin, 3.3% leuprolide and 86.8 triptorelin. 70.2 % had received concomitant treatment: 22.3% bicalutamide, 60.3% abiraterone, 68.8% docetaxel, 4.1% cabazitaxel. Men were observed for a median of 5.6 years (range = 33 days to 10 years). Cardiovascular adverse events occurred in 14 patients (11.5%) on ADT alone and in 23 (19.0%) on combination therapy. 26 (21.4%) Hypertension, 1 (0.8%) myocardial infraction, 1 (0.8%) atrial fibrillation, 2 (1.6%) had heart failure, 1 (0.8%) sudden cardiac death, 5 (4.1%) acute thrombo-embolism, 1 (0.8%) stroke. In subgroup-analyses of different combination treatments, Cardiovascular events were found to be significantly associated with combination of abiraterone with ADT (HR = 1.31, 95 % CI: 1.13 to 1.37; P &lt; 0.001). For men with a history of pre-existing CVD, CV events were more pronounced, 23.9% vs. 6.6% for men without pre-existing CVD. Conclusions: Metastatic prostate cancer patients often have pre-existing CVD and CVD-Risk Factors. Addition of abiraterone to ADT increase the risk of cardiovascular events. Physicians should monitor their patients in order to early detect any abnormality, and should encourage them to adopt a healthier lifestyle.
A pilot study of lenvatinib plus pembrolizumab in patients with advanced sarcoma.
Authors: Sujana Movva, Viswatej Avutu, Ping Chi, Mark Andrew Dickson, Mrinal M. Gounder, Ciara Marie Kelly, Mary Louise Keohan, Paul A. Meyers, Seth M. Cohen, Martee Leigh Hensley, Jason A. Konner, Alison M. Schram, Robert A Lefkowitz, Joseph Patrick Erinjeri, Li-Xuan Qin, Tiffany Salcito, Kenneth Seier, William D. Tap, Sandra P. D'Angelo
Journal: Journal of Clinical Oncology (2023)

11517 Background: New treatment options are needed for sarcomas. Lenvatinib (L) is an oral, multi-tyrosine kinase inhibitor with significant inhibitory activity against VEGF receptor (VEFGR) 1-3, FGF receptor (FGFR) 1-3, KIT, platelet-derived growth factor receptor (PDGFR) alpha/beta, and RET. Experimental models suggest that L can favorably alter the tumor immune environment, and the combination of L and pembrolizumab (P) has proven to be synergistic and effective across multiple solid tumor types, providing rationale for this study. Methods: This is a pilot study evaluating the efficacy of L and P in select sarcomas. Patients who had at least 1 prior regimen but ≤ 3 were enrolled into one of five cohorts (n = 10 each) A: leiomyosarcoma (LMS); B: undifferentiated pleomorphic sarcoma (UPS); C: angiosarcoma and epithelioid hemangioendothelioma (EHE); D: synovial sarcoma (SS) and malignant peripheral nerve sheath tumor (MPNST); and E: osteosarcoma (OS) and chondrosarcoma (CS). Patients were treated with an initial 2-week run-in of L 20 mg orally daily. Subsequently, P was administered at 200 mg IV every 21 days. The primary endpoint for each cohort was the best objective response rate (ORR) documented by RECIST v1.1 by 27 weeks. The combination was considered worthy of further study if 2 or more responses were observed in a cohort. Secondary endpoints included progression-free survival (PFS), overall survival, duration of response, and safety of the combination. Archival tissue and on-treatment biopsies were collected. Results: As of January 31 st , 2023, cohorts A, D and E have completed accrual. The best response in the LMS cohort was stable disease (SD). In cohort D there were 3 partial responses (PR): 2 SS; 1 radiation associated high grade MPNST. In cohort E one of 6 patients with OS had a PR. To date, of the 6 patients with angiosarcoma, there was 1 PR in a patient with adrenal primary that occurred after the prespecified 27-week timepoint. One of 5 evaluable patients in Cohort B had a PR. Among the 44 patients evaluable for safety, most common AEs were hypertension (56.8%), diarrhea (45.5%), proteinuria (45.5%), fatigue (40.9%), headache (36.4%) and nausea (36.4%). Most common ≥ grade 3 AEs were hypertension (13.6%), dyspnea (6.8%), non-cardiac chest pain (6.8%), syncope (6.8%). Conclusions: A signal of activity was noted in this pilot study for patients with OS, MPNST, angiosarcoma and SS. In the LMS cohort, there were no responses, and PFS was poor. Enrollment to cohorts B and C is ongoing. Clinical trial information: NCT04784247 . [Table: see text]